Leora Horn, BSc, MSc

Over three hundred thousand Canadians currently suffer from Alzheimer's disease (AD) and the related dementias. AD is a degenerative disorder associated with a progressive decline in cognitive function. There is significant neuronal loss and impairment of metabolic activity in the cerebral cortex, hippocampus and subcortical structures affecting memory, language and emotion. At present, there are limited drugs used to treat the symptoms associated with the disease but there is no cure. In a recent Nature publication, Schenk et al., reported results that take the treatment of AD in a new direction by raising the possibility of vaccination as prevention against disease development. In two separate sets of experiments scientists were able to prevent the occurrence or reduce the presence of Alzheimer-like pathology in genetically engineered mice immunized with one of the proteins that may be responsible for disease evolution.¹

According to the Alz-heimer's Association of Canada, AD is the fourth leading cause of death in adults. The prevalence of AD increases exponentially with age. AD affects 1 in 100 Canadians between the ages of 65 and 74, 1 in 14 Canadians between the ages of 75 and 84 and 1 in 4 Canadians over 85. Symptoms of AD range from forgetfulness to disorientation to people, time and place resulting in an inability to function without assistance.

Eleanor Brownridge

Until recently, many general practitioners have been hesitant to diagnose Alzheimer's Disease (AD), especially at the mild and moderate stages. They believe that patients and their families don't want to hear this bad news and therefore don't push the issue.

"We have to work hard to change the attitudes of physicians," says Dr. Ron Keren, geriatric psychiatrist with the University Health Network, Toronto General Hospital. "We have to move away from stigmatizing Alzheimer's and start approaching it as any other serious disease. We need to talk frankly, openly and honestly with our patients." Research from the United States has shown that 80 percent of seniors want to know if they have dementia. Dr. Keren, who also practices at the Toronto Rehabilitation Institute and the Whitby Health Centre, says that in over seven years he has never had a patient who didn't want to know the state of his disease. "If you can't talk about it, how can you treat it?"

With the recent decisions of Ontario and Manitoba to reimburse donepezil (Aricept) in those provinces, physicians now have a treatment for mild to moderate dementia of the Alzheimer's type that can bring hope to all patients and their families, not just those who can afford it.

Donepezil inhibits the activity of acetylcholinesterase, thereby increasing levels of acetylcholine in the brain.

Donepezil (Aricept), is now being reimbursed to eligible Ontario patients by the Ontario Drug Benefit Program. Donepezil received Health Protection Branch (HPB) approval in August 1997. Until now, however, donepezil has not been reimbursed by any provincial health plan, including Ontario's public drug program which covers senior citizens and those on social assistance. People wanting donepezil have had to pay for it themselves or have it reimbursed by private insurance.

Effective June 1, 1999, eligible ODBP beneficiaries will have the cost of donepezil reimbursed. There are two categories of coverage. Those who have already been on donepezil treatment for more than 60 days, have a confirmed diagnosis of mild to moderate AD and meet the ODBP program criteria will be eligible for reimbursement of donepezil by the ODBP.

Others with a confirmed diagnosis and who meet the ODBP and program criteria but who have never taken donepezil (or have taken it for less than 60 days) will be enrolled in a 12-week trial prescription program, with the medication provided free of charge by Pfizer. The trial prescription program is administered by an independent pharmacy and healthcare company, Caremark Ltd., based in Mississauga, Ontario.

The patient and caregiver also will receive a Pfizer-sponsored program of educational material about AD, including a video, called TriAD and a patient diary. The physician will continue to be supplied with diagnostic and other support tools to help him or her evaluate and track the patient's progress.

At the end of the 12-week trial prescription program, those patients who have benefited from the treatment will be eligible for continuing treatment reimbursed by the Ontario government. All patients receiving reimbursement will be reviewed annually to ensure they are still benefiting from the treatment and thus remain eligible for reimbursement.

The major instrument used to measure eligibility and effectiveness will be the Mini Mental Status Exam (MMSE). A score of 30 represents full cognitive ability; persons with impairment caused by AD score lower and their scores diminish over time as the disease takes its toll on cognitive function.

To be eligible for coverage, persons with mild to moderate AD will have to have and maintain an MMSE score between 10 and 26. A score that drops below 10 is indicative of advanced cognitive impairment of the later stages of AD, for which treatment with donepezil would not be appropriate.

Patients, caregivers or healthcare professionals seeking more information about reimbursement for donepezil can call toll-free to 1-800-510-6141.

Warren T Blume, MD, FRCP(C)
Professor, Department of Clinical Neurological Sciences, Director, EEG Laboratory,
London Health Sciences Centre, London, Ontario

Presented with an elderly patient exhibiting apparent cognitive decline, the physician must address three questions: (1) Does the decrease in apparent intellectual performance represent true dementia or pseudo-dementia? (2) Is there a treatable etiology? and (3) What is the prognosis? Of the diagnostic tests that society can afford, a well performed EEG can answer these questions as well as any test--after a thorough functional enquiry and physical examination.

Diffuse, persistent, excess delta (1-3 Hz) activity in this awake 75 year old man with cognitive decline.

Alzheimer's disease, a principal cause of dementia in the elderly, can produce several EEG abnormalities: a slowing of background rhythms, the appearance of diffuse slow-waves, triphasic waves, and a lack of clear EEG distinction between wakefulness, drowsiness, and light sleep. Rae-Grant et al. found a true dementing illness in 38 of 39 elderly subjects when such features appeared persistently in the recording and in 31 of 39 in whom they appeared intermittently.

Extracts from the leaves of the Ginko biloba tree and Vitamin E are just two of the therapies being investigated for the treatment of Alzheimer's Disease

Neil Fam, BSc, MSc

Alzheimer's Disease (AD) is a chronic neurodegenerative disorder characterized clinically by a gradual onset of progressive memory loss with deterioration in patients' social and occupational function. Changes in mood, behaviour and perception are also problematic aspects of the disease. Neuropathologically, AD is associated with the formation of amyloid plaques and neurofibrillary tangles, with impaired synaptic function and neuronal cell death. In particular, patients with AD suffer the loss of cholinergic, noradrenergic and dopaminergic neurons. Loss of acetylcholine neurotransmission in brain areas involved in learning and memory is thought to underlie many of the cognitive symptoms of AD. This concept forms the basis of current therapeutic strategies which aim to increase available acetylcholine levels in the brain by inhibition of acetylcholinesterase.

Olya Lechky

Making the home safe and secure for people with Alzheimer's Disease (AD) is one of the biggest challenges confronting families and caretakers.

Protecting people with AD from physical hazards and providing them with emotional and psychological security is a fine balancing act, says Linda LeDuc, director of support services for the Alzheimer Society of Canada in Toronto. The key is to find a way to optimize safety and security, while fostering as much independence and dignity as possible according to a person's cognitive abilities.

Simple, small changes are usually enough to create a safe environment that remains familiar and comforting. Stripping the home of all potential hazards can create a bleak, depressing and frustrating environment that may prematurely foster dependence. "If a person can still safely use a knife to cut bread, there's no point in stripping the kitchen counters bare," says LeDuc. "It can be very frustrating if the person wants to cut a bagel and can't find a knife."

Safety and security issues are of paramount importance to the 29% of people with AD who live alone, supported by family, friends, paid workers and volunteers. Of concern are the periods of time when the person is alone, most frequently at night.

Olya Lechky

Dr. Gauthier, director of the Alzheimer's Disease research unit at the McGill Centre for Studies in Aging in Montreal, has been immersed in AD research for over two decades. He has published 175 scientific papers in a host of scientific journals and was the editor of 52 contributions to a textbook called The Clinical Diagnosis and Management of Alzheimer's Disease. "This is the number one textbook on AD in the world right now. So Canada is very much in the forefront in this field.

Research and Practice in Alzheimer's Disease: 1996
Editors: B. Vellas, J. Fitten, G. Frisoni Serdi Publisher, Paris, 1998.

Reviewed by: Barry J. Goldlist, MD, FRCPC, FACP
This book has been developed in a "yearbook" type format. However, instead of reviewing key articles in the literature, it is composed of invited articles. This of course makes it more like a textbook, with the inevitable problems of keeping it up to date. However, unlike a textbook, there is not a common theme or progression of content.

Nevertheless, this is a worthwhile text. Even if some of the articles in the first section (research in Alzheimer's disease) are not on the cutting edge, there is useful information for the practitioner in the field. The second section (practice in Alzheimer's disease) is particularly successful because of its international flavor. The articles are wide ranging, and include a good review of dementia with Lewy bodies, and interesting articles on how environmental manipulations might affect behavior in dementing disorders.

The editorial that introduces the text suggests that it would be of interest to a wide range of professionals involved with Alzheimer's disease, including primary care physicians. My guess is that its greatest appeal will be for clinicians heavily involved with dementia diagnosis and care, such as geriatricians, geriatric psychiatrists, and neurologists.

The Alzheimer Society announced August 18th a commitment of over $1.2 million to further the cause of Alzheimer research in Canada. Since 1989, the Society has funded both biomedical and psychosocial research in an effort to find a cause and cure for the disease and find improved methods of caregiving and delivering services to people affected by Alzheimer Disease (AD).

Dr. Marilyn Miller of McGill University in Montreal is one of the 20 researchers across Canada receiving funding. Dr. Miller is investigating the role that estrogen plays in AD. Alzheimer Disease affects more women than men and affected women score lower than men in performance scores. Previous research has indicated that women given estrogen replacement therapy showed improved cognitive function. Dr. Miller seeks to determine why this occurs and whether estrogen could be used as a treatment for the disease.

In an effort to enhance care for those with AD, Dr. Marian Campbell of the University of Manitoba in Winnipeg will use her grant to research eating and feeding issues of people with AD. Those with the disease are at risk of malnutrition and weight loss because of under consumption of food and liquids. Eating-related difficulties contribute to these problems and can make meals difficult and emotionally taxing for both the caregiver and the person with the disease. Dr. Campbell's research will examine the challenges encountered and strategies used by caregivers in the home to determine how food preparation, environmental adaptations and the promotion of independence in eating can enhance the eating experience of people with AD.

Other projects the Society is funding include research on the role of anti-inflammatory drugs, amyloid-beta protein, managing challenging behaviours and reducing vehicle crash injuries.

While the Society's $1 million commitment to research is significant, Alzheimer research in general remains severely underfunded. "There is such potential for Alzheimer research in this country; Canadians are leaders in Alzheimer research", says Dr. Peter Scholefield, Chair of the Research Policy Committee of the Alzheimer Society of Canada. "Unfortunately, funding is not keeping up with the need. Especially with the aging baby boom population, there is an urgent and immediate need for more Alzheimer research funding."

Funding for the Joint Alzheimer Society Research Program includes contributions from provincial and local Alzheimer Societies across Canada, individuals, and corporations including key leadership gifts from Bayer Healthcare, Extendicare Health Services and the Royal Bank of Canada Charitable Foundation.

For a complete listing of the 1998-1999 research grants and awards, look under "Research", then "Research Program" on the Alzheimer Society of Canada Web site: www.alzheimer.ca or call Debbie Krulicki at (416) 488-8772 ext. 232.

Barry J. Goldlist MD, FRCPC, FACP

The first five international conferences on Alzheimer's Disease were meant for scientists, as there was essentially nothing available for clinical use. This year's meeting was quite different. The recent licensing of donepezil in Canada and the United States will soon be followed by numerous new drugs, many of which will have novel modes of action. The importance of Canadian research in this field was highlighted by the active participation in the program of Howard Feldman (Vancouver), Serge Gauthier (Montreal) and Ken Rockwood (Halifax). One of the keynote presentations was by Peter St. George Hyslop, Director of the Centre for Research in Neurodegenerative Disorders at the University of Toronto.

The meeting still emphasized basic science, particularly in the area of molecular genetics and molecular biology, but there were more than enough sessions for clinicians and clinical investigators. One interesting symposium concerned itself with the design of clinical trials for demonstrating disease course-altering effects (rather than just symptomatic improvement). It seems that for the immediate future, staggered start and withdrawal design will be the standard. The theory is that if a drug truly alters the disease course, patients starting the active drug later (i.e. placebo changed to active drug) will never achieve the same benefit as the group started on active drug (i.e. active drug to active drug). Similarly, early withdrawal patients (i.e. active drug changed to placebo) would have a better end result than patients never on active drug (placebo to placebo). Preliminary evidence was presented that suggested a new drug, propentofylline, might have such an effect. This drug is not a cholinesterase inhibitor such as donepezil, but rather is felt to be a microglial cell modulator, and thus inhibits some of the inflammatory response seen in various dementias.

Farther from clinical applicability, but still exciting was a round table discussion entitled "Beyond Cholinesterase Inhibitors: Toward the Next Generation of AD Therapeutics." Presentations on possible therapeutic interventions, such as modulating b-amyloidogenesis, inhibiting neurofibrillary degeneration or using muscarinic agonists. It seems quite likely that the 7th International Symposium in the year 2000 will be even more exciting for clinicians.